We present a case of progressive disseminated aspergillosis that involved multiple sites in a bone marrow transplant recipient with severe, chronic graft-versus-host disease. The patient failed to respond to treatment with a conventional dosage of a lipid formulation of amphotericin B (lifoAmB; 5 mg/kg/day) given alone or in combination with itraconazole, and he responded only to an aggressive strategy that included a very high dosage of lifoAmB (15 mg/kg/day) given in combination with itraconazole as well as a rapid reduction in immunosuppression. Despite the patient's abnormal baseline kidney function, the very high doses of lifoAmB were well tolerated and did not result in additional renal toxicity.